Clear all

What are mTORC1 and Rapamycin and How do They Extend Longevity?  

Posts: 36
Joined: 1 year ago

What are mTORC1 and Rapamycin and How do They Extend Longevity?

Lessons from David Sabatini — the world’s expert on mTOR

Your body is the craziest piece of technology you own. More than the Internet that connects the world, the transistors that power phones and computers, or artificial intelligence embedded in the products we use.

Recently, I have been really interested in the molecular biology of our body and how it changes as we age. Only after researching this topic have I gained a true appreciation for how complex and numerous the biological pathways that comprise our body are.

Even though our body as a whole is more powerful/complex than the average computer, a computer makes a very nice analogy to our body. The cells and all the different organelles are like the hardware of our bodies. The biological pathways that transmit signals from organelle to organelle are the software of our body.


An analogy of the body to a computer

Understanding the software of our bodies is key to understanding problems that go back to my motivation: the aging process. One key node that affects several biological pathways all relevant to aging is called mTORC1. mTORC1 and the molecule that inhibits it — rapamycin — have received a lot of attention from the longevity community and I have spent the past week trying to understand its importance to the function of our cell and why altering it has such a large effect on lifespan.

Discovery of mTORC1 and Rapamycin ?


The famous statues are characteristic of Easter Island where Rapamycin was discovered ?

Rapamycin was first discovered in a soil sample in 1972 on Easter Island, colloquially known as Rapa Nui which is where the name rapamycin comes from. At the time researchers could test what rapamycin did — they found it was a useful immunosuppressant — but they did not know what it’s protein target was.

Decades later in a lab at Johns Hopkins work took place to learn what the protein target of rapamycin was. The work of David Sabatini who was a graduate student discovered and sequenced the target — a protein known as mTOR (mammalian target of rapamycin). More info on how he discovered mTOR can be found in his lecture on mTOR if you are curious.

An important thing they learned about mTOR is that it was a kinase. A kinase is a protein that phosphorylates (adds a phosphate group) to an amino acid. This is important because the phosphate group basically acts as a flag telling other proteins to bind on top of the phosphate.


What mTORC1 looks like as a protein

What they later found is that mTOR is part of a protein complex called mTORC1. A protein complex is simply a group of proteins that are linked (non-covalently) to perform a common function.

Functions of mTORC1

This is very important so I think it is necessary to repeat. The main function of mTORC1 is the regulation of growth.


High level of what mTORC1 does/regulates

Information that mTORC1 takes in (Also known as upstream effects):

  • nutrients in the form of amino acids (leucine, arginine, and lysine specifically)
  • growth factors/hormones like insulin. (other cells in the body telling the cell to grow)
  • energy levels — ATP.
  • DNA damage (p53) can inhibit mTORC1

At a high level, mTORC1 takes in all of this information from the cell through different binding sites in the complex. With this information, it can make decisions on what functionalities to do.


All of the downstream effects of mTORC1

Things that mTORC1 can do (Also known as downstream effects) :

  • phosphorylate p70S6K which later effects pyrimidine synthesis (nucleotide synthesis), ribosome activation, polypeptide translation, and synthesis in the ribosome. All of the ribosomal effects positively impact protein synthesis which is important for growth.
  • inhibits ULK1 which inhibits autophagy. Autophagy is the process where things are degraded in the cell. If you are trying to grow then you do not want this to happen.
  • inhibits TFEB which is a transcription factor for lysosomes the organelles that carry out autophagy. This also effectively inhibits autophagy.
  • inhibits Erk5 which inhibits proteasomal degradation.

All of the functions of mTORC1 promote growth. In fact,mTORC1 is known as the “master regulator of growth” because it is able to take input from so many different places and affect growth in many different ways. mTORC1 can sense when nutrients fluctuate and if they go down to a certain extent it can stop growth activating, what David Sinclair calls, the “survival circuit”.

Problems with mTORC1 As We Age


On the left is a proper functioning cell. Right is how cells act in old age.

If we go back to our computer analogy, you can think of mTORC1 as a logic gate to the computer of our body. It takes in all of the inputs and if they are all-sufficient it will turn on. What seems to be occurring, is that in our old cells the mTORC1 as an OR logic gate. If some of the processes to activate growth are necessary then it will be activated. In reality, it should be acting like a AND logic gate where both all of the inputs should be correct.


Another theory about mTORC1

Another main idea here is to basically take mTORC1 activity and reduce it to an optimal level. As you can see in the graph above the level of mTORC1 activity increase with problems like obesity/high-fat diet which promotes growth. Lifestyles like caloric restriction, which is closer to what evolutionarily are bodies were primed for, are closer to the global maxima of health.

By supplementing molecules like rapamycin we are trying to reduce the activity of mTORC1 to get close to that global maxima.

Rapamycin’s effect on mTORC1

Rapamycin inhibits mTORC1 — inhibiting the growth of the cell. This has a positive effect because it reverts the cell back to a proper condition of not growing and taking up resources instead of “hunkering down to survive”. This mechanism extends longevity. Also by inhibiting mTORC1, more autophagy happens so more waste of the cell is flushed away which is a good effect.

Through different peer-reviewed studies, it has been shown that rapamycin increases lifespan in mammalian model organisms up to 110%. Here is a link to a review article that cites some of the recent studies that have been done. This resource on Laura Deming’s (a prominent longevity investor) website has a list of companies working on developing rapamycin the drug as well as other small molecules that act like rapamycin called rapalogs.

A big company that was working on the TORC1 pathway was resTORbio but actually today they merged with Adicet Bio to focus on Car T Cell Therapy.


  • Rapamycin can inhibit mTORC1 and increase lifespan as shown in Animal models.

Join Us!

Psychedelic Therapy:

Psychedelic Drug Psilocybin Tamps Down Brain’s Ego Center plus Getting Closer to Nature, One Bite at a Time

Psychedelic Drug Psilocybin Tamps Down Brain’s Ego Center plus Getting Closer to Nature, One Bite at a Time – Dr. Frederick Barrett – Steve Brill – Violet Brill – Perhaps no region of the brain is more fittingly named than the claustrum, taken from the Latin word for -hidden or shut away-. The claustrum is an extremely thin sheet of neurons deep within the cortex, yet it reaches out to every other region of the brain. Its true purpose remains -hidden away- as well, with researchers speculating about many functions. What is known is that this region contains a large number of receptors targeted by psychedelic drugs such as LSD or psilocybin the hallucinogenic chemical found in certain mushrooms. To see what happens in the claustrum when people are on psychedelics, Johns Hopkins Medicine researchers compared the brain scans of people after they took psilocybin with their scans after taking a placebo. PLUS Steve and Violet Brill looks at a forest the same way most people think about a supermarket. Walkthrough a park or wooded area with them and they can show you a number of wild plants that might make for tasty additions to your dinner plate. They would tell you how yellow wood sorrel tastes just like lemonade or how black birch can be used as a minty flavoring for pudding. With the advent of this pandemic, foraging may be more important than ever. Some are including it in their home-schooling curriculum in hopes of arming their children with this almost-forgotten art.

Longevity – Life Extension – Anti-Aging Board



“An ounce of prevention is worth a pound of cure.”



Peptides – a Powerful Piece of the Longevity Puzzle

In this episode of Living Beyond 120, Mark and Dr. Gladden begin by talking about how we need to manifest goals in our minds first in order to make them realities.

Next, they discuss some recent health tests Dr. Gladden participated in, along with the remarkable results regarding his cardiovascular health and age. He talks about his plans for getting in the best shape of his life.

They continue their conversation revisiting the subject of peptides, discussing specific peptides, and the amazing outcomes that Dr. Gladden is seeing in his practice. From better immune function to healing the gut, improved fat burning, and much more, they describe which peptides have had positive health effects on many different conditions. To learn more about peptides, you can visit


The novel coronavirus causing COVID-19 seems to hit some people harder than others, with some people experiencing only mild symptoms and others being hospitalized and requiring ventilation. In this episode, Ted shares the latest research on the coronavirus.

Preventing Cardiovascular Disease – an Interview with Dr. Jeffry Life 

In this episode, we’re featuring a special RAAD Fest discussion from last year between Dr. Gladden and Dr. Jeffry Life, a doctor who has focused his practice on healthy aging and helping patients avoiding heart attacks and strokes. He incorporates the Bale-Doneen Method (learn more in the book Beat the Heart Attack Gene) in his treatment plans, which is about aggressively looking for vascular inflammation that causes heart disease and working to stop it.

They discuss some of the testings that can be done to identify vascular risk factors, which fall outside of the normal insurance-based model of healthcare.

Ketogenic Diet Hacks:

Doing The Perfect Keto Diet: Doing Perfect Keto – Chris Irvin –

Everyone agrees that a low-carb, low-sugar Keto lifestyle reduces inflammation and resets insulin sensitivity. Yet there is still confusion about what to eat too and what not to eat. So much so there are entire books dedicated to the subject. And much of that information in those books become outdated as soon as new research provides insights into which foods and supplements work or don’t work as originally expected. And when it comes to snack foods and sweet treats the water gets even murkier. What if there was a website that was driven by current science and gave you access to everything you needed to do low-carb Keto right? Perfect Keto.

RSS Live Long and Master Aging

  • #203 Health Starts In Your Mouth - Dr Dominik Nischwitz September 21, 2020
    Welcome to the Body Mind Empowerment podcast I’m your host Siim Land and our guest today is Dr Dominik Nischwitz. Dr Dome is a biological dentist and functional medical practitioner in Germany. He’s written the book It's All In Your Mouth and practices biological dentistry in his clinic. Timestamps: What Is Biological Dentistry 01:30 How […]
    Siim Land
  • #202 Birthday Q&A - Hair Health, Fixing Tendonitis, Preventing Neurodegeneration September 17, 2020
    This episode is a live Q&A on Siim's birthday. Timestamps: How to Improve HDL Cholesterol 01:53 Astragalus and Autophagy Boosters 02:55 Hair Health and Growth 04:29 How to Detox Regularly 05:53 Tips for Giving Up Caffeine 09:14 Siim's Current Food Protocol 10:48 Can Autophagy Fight the Virus 14:14 How to Treat Acne and Improve Skin […]
    Siim Land
  • #201 Molecular Hydrogen, Oxidative Stress, and Autophagy - Tyler LeBaron September 14, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Tyler LeBaron. Tyler is the founder and executive director of the Molecular Hydrogen Institute. He’s the world’s leading expert on molecular hydrogen and how it can affect health, aging, and stress resilience. Get Drink HRW Molecular Hydrogen for […]
    Siim Land
  • #200 Optimal Meal Timing and Circadian Rhythms - Siim Land at the Biohacker Summit 2019 September 12, 2020
    In this episode, you can listen to Siim Land's speech at the Biohacker Summit 2019 in Helsinki. It talks about optimal meal timing, circadian rhythms, and intermittent fasting. Click here to watch it on YouTube! Here are the links to the podcast on all platforms Link to the Audio Podcast on iTunes and Stitcher Link to the podcast […]
    Siim Land
  • #199 Why You Need More Magnesium to Manage Stress - Wade Lightheart September 6, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Wade Lightheart. Wade is one of the founders of BiOptimizers, which is a supplement company that fixes digestion. He’s also a Canadian natural bodybuilding champion. We’re going to talk about stress and magnesium. Timestamps: How Wade Reacted to […]
    Siim Land
  • #198 Stronger by Stress Q&A with Teemu Arina August 30, 2020
    In this episode of the Body Mind Empowerment Podcast we talk about my new book Stronger by Stress. It's recorded at the Biohacker Center with Teemu Arina. Timestamps: Introduction Notes 00:48 Siim's Time During the Lockdown 04:04 Hormesis and Antifragility 07:00 How to Lower Chronic Stress 10:35 Break Vicious Cycles of Stress 13:40 Gut Problems […]
    Siim Land
  • #197 Genetics for Weight Loss and Longevity - Joe Cohen August 25, 2020
    Welcome to the Body Mind Empowerment Podcast, I’m your host Siim Land and our guest today is Joe Cohen. Joe is the founder and CEO of Self-Hacked, which is one of the most popular biohacking websites online. He’s also founded SelfDecode, which is a genetics decoding company.   Timestamps: How Joe Started to Research Genetics […]
    Siim Land
  • #196 Neurohacking the Brain and Stress - Dr Greg Kelly August 19, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Dr Gregory Kelly. Dr Greg is a naturopathic physician and former editor of the journal Alternative Medicine Review. He’s also a lead product formulator at Neurohacker Collective. Timestamps: Greg's Background as an ND and the Army 02:10 Neurohacking […]
    Siim Land
  • #195 Continuous Glucose Monitoring for Better Metabolic Health - Kara Collier August 13, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Kara Collier. Kara is the Head of Nutrition at, which is a company that offers commercial continuous glucose monitoring services. Your glucose is one of the best indicators of overall metabolic health and flexibility. I also tried […]
    Siim Land
  • #194 Stoicism and the Art of Happiness - Donald Robertson August 5, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Donald Robertson. Donald is a writer about stoic philosophy and an expert in cognitive behavioral therapy. He’s written several books like How to Think Like a Roman Emperor and Stoicism and the Art of Happiness. Timestamps: How Donald […]
    Siim Land
  • #193 How to Stay Healthy in a City - Tim Gray July 31, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Tim Gray. Tim is an entrepreneur and biohacker from the UK. He’s also the founder of the Health Optimisation Summit in London. We’re going to talk about how to stay healthy and well when living in urban environments […]
    Siim Land
  • #192 Dr Dominic D’Agostino on Using Ketosis for High Stress Environments July 25, 2020
    Welcome to the Body Mind Empowerment podcast I’m your host Siim Land and our guest today is Dr Dominic D’Agostino. Dr Dom has a PhD in neuroscience and physiology. He’s a professor at the University of South Florida and is considered one of the world’s top experts in ketosis, ketogenic diets, fasting, and hyperbaric oxygen […]
    Siim Land
  • #191 Biohacking Focus, Productivity and Performance with Olli Sovijärvi and Teemu Arina July 19, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guests today are Olli Sovijärvi and Teemu Arina. Olli and Teemu run the Biohacker Center in Finland and organize the Biohacker Summit. In this episode we’re going to talk about how to optimize your health and performance at work, especially if […]
    Siim Land
  • #190 How to Swap Out Bad Fats From Your Body with Dave Asprey July 12, 2020
    Welcome to the Body Mind Empowerment Podcast. I’m your host Siim Land and our guest today is Dave Asprey. Dave is the founder of Bulletproof, Truedark, and many other companies. He’s a best-selling author of several books and often called the ’father of biohacking’. Timestamps: Biohacking and Medical Freedom 03:20 Bulletproof Coffee and Structured Water […]
    Siim Land
  • #189 Lower Inflammation and Pain Using PEMF Therapy with Bob Dennis PhD July 6, 2020
    Welcome to the Body Mind Empowerment Podcast I’m your host Siim Land and our guest today is Bob Dennis. Bob has a PhD in Biomedical Engineering. He’s one of the first people to use Pulsed Electromagnetic Frequency (PEMF) therapy in NASA. During the 90s he worked with NASA to build PEMF equipment for astronauts. Bob […]
    Siim Land

Please follow & like us :)